title: Overexpression of peptide deformylase in breast, colon, and lung cancers.
abstract: BACKGROUND
  Human mitochondrial peptide deformylase (PDF) has been proposed as a novel cancer therapeutic target. However, very little is known about its expression and regulation in human tissues. The purpose of this study was to characterize the expression pattern of PDF in cancerous tissues and to identify mechanisms that regulate its expression.
  
  
  METHODS
  The mRNA expression levels of PDF and methionine aminopeptidase 1D (MAP1D), an enzyme involved in a related pathway with PDF, were determined using tissue panels containing cDNA from patients with various types of cancer (breast, colon, kidney, liver, lung, ovarian, prostate, or thyroid) and human cell lines. Protein levels of PDF were also determined in 2 colon cancer patients via western blotting. Colon cancer cells were treated with inhibitors of ERK, Akt, and mTOR signaling pathways and the resulting effects on PDF and MAP1D mRNA levels were determined by qPCR for colon and lung cancer cell lines. Finally, the effects of a PDF inhibitor, actinonin, on the proliferation of breast, colon, and prostate cell lines were determined using the CyQUANT assay.
  
  
  RESULTS
  PDF and MAP1D mRNA levels were elevated in cancer cell lines compared to non-cancer lines. PDF mRNA levels were significantly increased in breast, colon, and lung cancer samples while MAP1D mRNA levels were increased in just colon cancers. The expression of PDF and MAP1D varied with stage in these cancers. Further, PDF protein expression was elevated in colon cancer tissue samples. Inhibition of the MEK/ERK, but not PI3K or mTOR, pathway reduced the expression of PDF and MAP1D in both colon and lung cancer cell lines. Further, inhibition of PDF with actinonin resulted in greater reduction of breast, colon, and prostate cancer cell proliferation than non-cancer cell lines.
  
  
  CONCLUSIONS
  This is the first report showing that PDF is over-expressed in breast, colon, and lung cancers, and the first evidence that the MEK/ERK pathway plays a role in regulating the expression of PDF and MAP1D. The over-expression of PDF in several cancers and the inhibition of cancer cell growth by a PDF inhibitor suggest this enzyme may act as an oncogene to promote cancer cell proliferation.
authors.affiliation: Department of Biological Sciences, North Dakota State University, Fargo, ND, USA.
authors.forename: Harsharan
authors.initials: H
authors.lastname: Randhawa
authors.forename: Shireen
authors.initials: S
authors.lastname: Chikara
authors.forename: Drew
authors.initials: D
authors.lastname: Gehring
authors.forename: Tuba
authors.initials: T
authors.lastname: Yildirim
authors.forename: Jyotsana
authors.initials: J
authors.lastname: Menon
authors.forename: Katie M
authors.initials: KM
authors.lastname: Reindl
mesh_terms: D000581:Amidohydrolases / Q000032:analysis / Q000096:biosynthesis*; D000626:Aminopeptidases / Q000032:analysis / Q000096:biosynthesis; D014408:Biomarkers, Tumor / Q000032:analysis*; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000378:metabolism*; D003110:Colonic Neoplasms / Q000378:metabolism*; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000378:metabolism*; D008297:Male; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000502:physiology; D046888:Tissue Array Analysis
chemical_list: D014408:Biomarkers, Tumor; D000626:Aminopeptidases; C511921:METAP1D protein, human; D000581:Amidohydrolases; C084507:peptide deformylase